The present invention relates to a device for taking up and/or releasing liquid samples according to the preamble of independent claim 1 and systems which include one or more such devices.
It is known that droplets with a volume of more than 10 xcexcl can be dispensed from the air very easily, since if the pipette is correctly manipulated, the droplets leave the pipette tip of their own accord. The droplet size is then determined by the physical properties of the sample liquid, such as surface tension or viscosity. The droplet size thus limits the resolution of the quantity of liquid to be dispensed.
The aspirating and dispensing, i.e. the pipetting of liquid samples with a volume of less than 10 xcexcl, in contrast, typically requires instruments and techniques which guarantee the dispensing of such small samples. The dispensing of a liquid using a pipette tip, i.e. using the endpiece of a device for aspirating and/or dispensing sample liquid, can occur from the air (xe2x80x9cfrom airxe2x80x9d) or by touching a surface. This surface can be the solid surface of a container (xe2x80x9con tip touchxe2x80x9d), into which the liquid sample is to be dispensed. It can also be the surface of a liquid in this container (xe2x80x9con liquid surfacexe2x80x9d). A mixing procedure following the dispensing is recommendedxe2x80x94particularly for very small sample volumes in the nanoliter or even picoliter rangexe2x80x94so that uniform distribution of the sample volume in a reaction liquid is ensured.
Disposable tips significantly reduce the danger of unintentional transfer of parts of the sample into a container (contamination). Simple disposable tips are known (xe2x80x9cair-displacement tipsxe2x80x9d), whose geometry and material is optimized for the exact aspiration and/or dispensing of very small volumes. The use of so-called xe2x80x9cpositive-displacement tipsxe2x80x9d, which have a pump plunger inside, is also known. Two procedures must be differentiated from one another for the automation of the pipetting process of volumes less than 10 xcexcl: the defined take-up (aspiration) and the subsequent release (dispensing) of liquid samples. The pipette tips are typically moved by the experimenter or a machine between these procedures, so that the aspiration location of a liquid sample is often different from its dispensing location. Only the liquid system, which includes a pump (for example a diluter implemented as a syringe pump), liquid line, and endpiece (pipette tip), is essential for the correctness and reproducibility of aspiration and/or dispensing.
A device and a corresponding method are known from U.S. Pat. No. 5,763,278. They involve automatic pipetting of small volumes, the device including a pipetting needle, a diluter with a liquid outlet having a syringe, and a valve. The syringe includes a piston and a piston drive. A line connects the needle and the liquid outlet of the diluter, the diluter and the line containing an essentially incompressible liquid. A pulse generator is positioned in the device and connected to the incompressible liquid in the line so that mechanical pulses with a force of at least 0.01 Ns can be emitted directly into the liquid of the line. A pulse of this type is used to drive liquid out of the needle. The droplet size is defined by a targeted advance of the diluter piston and the droplet is ejected from the needle using a pulse. Because the volume is defined using the diluter, the droplet size and its reproducibility is a function of the resolution of the diluter and is limited thereby.
A pipetting device which includes a piston pump and a pulse generator in the form of a piezoelectric element is known from Japanese Patent 09 327628. The piezoelectric element is also the front plate of the piston and is used for terminating the dispensing procedure. The piston causes the majority of the liquid dispensing through its downward movement and is blocked during the actuation of the piezoelectric plate. The movement direction of the piezoelectric plate corresponds in this case to that of the piston. At least a part of the volume dispensed thus always depends on the movement of the piston, so that the reproducibility of the piston movement limits the resolution of the pipetting device.
From WO 97/15394 a multiwellplate called there as xe2x80x9cJetWellxe2x80x9d is known with wells that have an larger upper opening and a nozzle-like opening below. When a pressure pulse is exercised to the surface, a jet of liquid is ejected through each one of these nozzles. Selecting the duration of such a pressure pulse defines the volume of the ejected liquid. Larger volumina cannot be pipetted or dispensed this way.
A sample dosage system, according to the species, comprising an injection needle which is linked to a stationary dosage pump as well as to an also stationary liquid reservoir is known from DE 43 18 919. A sample dosage system for being applied to liquid chromatography is disclosed. This system comprises switching means with which it is possiblexe2x80x94in a first position of the switching means and by closing the injection needlexe2x80x94to make a connection between the liquid reservoir and the dosage pump. In a second position of the switching means it is possible to lift off the injection needle and to separate the reservoir for the flushing fluid from the dosage pumpe. This switching means are implemented basically as some sort of three-way valves and provide for the flushing of the injection needle andxe2x80x94by pulling back the pistonxe2x80x94also of the cylinder.
The object of the present invention is to suggest an alternative device of the type initially cited for aspirating and/or dispensing liquid samples down into the picoliter range, which allows the flushing of the cavity via a flush inlet which is independent of the pipette tip.
This object is achieved according to the present invention in that a device for aspirating and/or dispensing liquid samples is suggested which corresponds to the features of independent claim 1. Further preferred features result from the dependent claims.
Such a device for aspirating and/or dispensing liquid samples has the advantage that it may be constructed in a very space-saving way, so that a system for aspirating and/or dispensing samples of a liquid may include one single device, but preferably many such devices, which may be positioned in linear groups or in two-dimensional arrays. Such systems are preferably automated and therefore capable of processing large numbers of samples. For the purpose of rationalizing the cycles, such systems are preferably equipped with a robot device which may move the devices in the X and/or Y and/or Z directions. Due to the multiple devices arranged in an array, the liquid samples may be dispensed at the xe2x80x9cwellsxe2x80x9d of microplates, which are also known as microtitration plates (trademark of Beckman Coulter, Inc. 4300 N. Harbour Blvd., P.O. Box 3100 Fullerton, Calif. 92834, USA).